Proliferation and significance of clinically relevant β-lactamases
Proliferation and significance of clinically relevant β-lactamases
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DOI：
10.1111/nyas.12023
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发表时间：
2013-01-01
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影响因子：
--
通讯作者：
Bush, Karen
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作者：
Bush, Karen
细菌感染中β-内酰胺酶对β-内酰胺抗生素的灭活与目前遇到的一些最严重的感染性疾病问题有关。独特的β-内酰胺酶的进化导致在天然临床分离株中鉴定出1，300多种不同的酶。在这些酶中，最有害的β-内酰胺酶是超广谱β-内酰胺酶或ESBLs，其水解大多数青霉素和头孢菌素，以及碳青霉烯酶，其可降解所有β-内酰胺类药物。世界上最主要的ESBLs是CTX-M-14和CTX-M-15酶。在酶家族中，TEM和OXA β-内酰胺酶表现出最大数量的变体。碳青霉烯酶的广泛组特别危险，特别是KPC丝氨酸碳青霉烯酶和金属β-内酰胺酶的NDM家族，这两种酶都出现在通常对大多数类别的抗生素具有耐药性的多重耐药革兰氏阴性病原体中。尽管正在研究新的β-内酰胺酶抑制剂组合作为控制由这些生物体引起的感染的手段，但迫切需要其他方法。
Inactivation of beta-lactam antibiotics by beta-lactamases in bacterial infections is associated with some of the most serious infectious disease issues that are currently encountered. The evolution of unique beta-lactamases has resulted in more than 1,300 distinct enzymes that have been identified in natural clinical isolates. Of these enzymes, the most deleterious beta-lactamases are the extended-spectrum beta-lactamases, or ESBLs, that hydrolyze most penicillins and cephalosporins, and the carbapenemases that may inactivate all beta-lactam classes of drugs. The most prominent ESBLs worldwide are the CTX-M-14 and CTX-M-15 enzymes. Among enzyme families, the TEM and OXA beta-lactamases exhibit the greatest number of variants. The broad groups of carbapenemases are particularly treacherous, especially the KPC serine carbapenemases and the NDM family of metallo-beta-lactamases, both of which appear in multidrug-resistant Gram-negative pathogens that are often resistant to most classes of antibiotics. Although new beta-lactamase inhibitor combinations are being investigated as a means of controlling infections caused by these organisms, additional approaches are sorely needed.